Biomedical subjects
Publications and source records attributed to H D Röher.
Mild injuries to the head are a common everyday occurrence. Only one out of 30,000 patients suffering mild traumatization of the brain subsequently goes on to develop a complication that requires treatment. Such patients can be identified on the basis of the Glasgow Coma Scale and the determination of risk factors, and these data also serve as an aid for deciding whether surveillance at home or hospitalization is indicated.
AIM: To investigate the role of coding region mutation and promoter hypermethylation of TP53 in adrenocortical cancer formation. METHODS: Twenty sporadic adrenocortical cancers (ACCs) and five normal adrenal tissue samples were available for analysis. Coding region mutation of TP53 in 20 ACCs was examined by polymerase chain amplification using intronic primers for exons 2-11 and direct sequencing of the product. In 10 ACCs and five normal adrenal tissue specimens, methylation of the 16 CpG sites within the TP53 promoter was examined using bisulphite methylation sequencing. RESULTS: Coding region mutation in TP53 was demonstrated in 5 of 20 ACCs. There were four mis-sense mutations and one frameshift mutation. Four of 5 patients with a TP53 mutation had metastases at diagnosis or detected soon thereafter and 3 of 4 died of disease within 12 months of surgical resection. No methylation was seen in the TP53 promoter in 10 ACC and the five normal adrenal tissues examined. CONCLUSION: Coding region mutation in TP53 occurs in 25% of ACCs with a trend toward a poorer prognosis. Promoter methylation of TP53 is not present in ACC as a mechanism for tumour suppressor gene (TSG) inactivation and, therefore, other genes in the 17p13 region are implicated in adrenal carcinogenesis.
INTRODUCTION: Decreasing the length of stay is a possible means of cost control in the medical system. Therefore we performed a study to test the feasibility of reducing hospital stay to 2 days after thyroid operation. METHODS: In a controlled prospective trial, 238 patients were randomly assigned to group A (2 days of stay) or group B (more than 2 days). Studied were medical standard, practicability, patient acceptance, and quality of life. RESULTS: Of those in group A, 56.6% did not leave the hospital at the scheduled 2nd day post operation. Reasons were preoperative hyperthyroidism ( P<0.011), postoperative hypocalcemia ( P<0.03), or unspecific disturbances. In group B, 28% of the patients left before the established borderline of 3-4 days, and only 35% left on the 2nd postoperative day. CONCLUSION: Reduced length of stay has no negative influence on medical standards. The quality of life of patients leaving the hospital on the 2nd postoperative day was significantly higher. Reducing hospital stay after thyroid operation to 2 postoperative days is desirable and possible without a loss in quality of care, except in case of postoperative complications or unspecific complaints.
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Differentiated thyroid cancer is a malignant tumour that has a fairly good prognosis, with patients surviving for many years. Multimodal therapy with surgery, radioiodine therapy and TSH suppressive medication is of proven efficacy. However, loss of differentiation is observed in up to one-third of patients with differentiated thyroid cancer, paralleled by an increase in tumour grading and loss of thyroid-specific functions (thyrotropin receptor, iodine accumulation). Such tumours may no longer be amenable to standard treatment protocols, including TSH suppression and radioiodide therapy. Retinoic acids have been shown to exert re-differentiating effects on thyrocytes in various experimental studies and case reports, and it was on this basis that this pilot study was initiated. Patients with advanced thyroid cancer and without the therapeutic options of operation or radioiodide therapy were treated with 13- cis-retinoic acid at a dosage of 1.5 mg/kg body weight daily over 5 weeks. Parameters for assessment of the therapeutic effect were serum thyroglobulin (TG) levels, radioiodine uptake, and tumour size prior to and after retinoid treatment. Fifty patients were evaluated for response, classified as reduction in tumour size and TG levels, stable disease or disease progression. Thirteen patients showed a clear increase in radioiodine uptake, and eight a mild increase. TG levels were unchanged or decreased in 20 patients. Tumour size was assessable in 37 patients; tumour regression was observed in six, and there was no change in 22. In total, a response was seen in 19 patients (38%). Response to retinoid therapy did not always correlate with increased radioiodine uptake, so other direct antiproliferative effects have to be assumed. The encouraging results of the study and the low rate of side-effects with good tolerability of retinoids warrant further studies with altered inclusion criteria and employment of other redifferentiating drugs or combinations of agents.
The diagnostic procedure is determined by the severity of the diverticulitis. In complicated cases of diverticulitis, it is necessary to detect those patients with obstructive ileus, perforation, and peritonitis who require instant emergency surgery. In all other cases, diagnostic procedures serve as a tool to determine the best therapeutic options. The CT scan of the abdomen seems to have the highest reliability for determining therapy. Other investigations such as barium enema and coloscopy are not indicated in emergency cases or cannot exactly describe the stage of the diverticular disease. Many surgeons still prefer an enema with water-soluble contrast medium in emergency cases to visualize a perforation. CT scans have the same ability to answer this question, but they are more expensive and are not available everywhere at any given time.
BACKGROUND AND AIMS: This study compared two histopathological examinations for the diagnosis of neurogenic appendicopathy (NA), assessed the frequency of NA, and evaluated whether it is a clinical disease entity distinct from acute appendicitis. PATIENTS AND METHODS: In a prospective observational multicenter study (surgical departments of five hospitals with one reference pathology) we evaluated 282 patients who underwent appendectomy for suspected appendicitis; we examined the frequency of NA in acute appendicitis and in the negative appendectomy group. For the diagnosis two staining methods were compared. We also attempted to determine clinical features of NA. RESULTS: We observed 93% accuracy for hematoxylin-eosin staining compared with S-100 staining (reference standard) in the diagnosis of NA. There was NA in 3.8% of patients with acute appendicitis and in 47% of those with negative appendectomy. We observed significant differences between the three groups (NA without appendicitis, acute appendicitis, and negative appendectomy without neurogenic appendicopathy) only for sex, age, vomiting, similar previous complaints, rebound tenderness, guarding, rigidity, leukocytes (univariate analysis) and sex (multivariate analysis). CONCLUSION: Neurogenic appendicopathy is a histopathological entity that can be identified by hematoxylin-eosin staining. History and clinical examination do not enable us preoperatively to differentiate between acute appendicitis, NA, and negative appendectomy.
BACKGROUND: The effectiveness of neoadjuvant treatment (NT) prior to resection of squamous cell carcinoma of the esophagus (SCCE) in terms of prolonged survival has not been proven by randomized trials. Facing considerable financial expenses and with concerns regarding the consumption of the patient's remaining survival time, this study aims to provide rationales for pretreating resection candidates. METHODS: From March 1986 to March 1999, patients undergoing resection for SCCE were documented prospectively. Since 1989, NT was offered to patients with mainly upper and middle third T3 or T4 tumors or T2 N1 stage who were fit for esophagectomy. Until 1993, NT consisted of chemotherapy. Since that time chemoradiation has also been applied. The parameters for expense and benefit of NT are costs, pretreatment time required, postoperative morbidity and mortality, clinical and histopathological response, and actuarial survival. RESULTS: Two hundred and three patients were treated, 170 by surgery alone and 33 by NT + surgery. Postoperative morbidity and mortality were 52% to 30% and 12% to 6%, respectively (p = n.s.). The response to NT was detected in 23 patients (70%). In 11 instances (33%), the primary tumor lesion was histopathologically eradicated. Survival following NT + surgery was significantly prolonged in node-positive patients with a median survival of 12 months to 19 months (p = 0.0193). The average pretreatment time was 113 +/- 43 days, and reimbursement for NT to the hospital amounted to Euro 9.834. CONCLUSIONS: NT did not increase morbidity and mortality. Expenses for pretreatment, particularly time and costs, are considerable. However, taking into account that the results are derived from a non-randomized study, patients with regionally advanced tumor stages seem to benefit, as seen by their prolonged survival.
Postoperative peritonitis carries a higher risk of complications and mortality than does community-acquired disease. Little, however, is known about the specific microbiology of this condition. To gain insight into this problem, the microbiological findings of 67 patients with postoperative peritonitis were compared with those of 68 patients with community-acquired peritonitis. In a comparison of postoperative peritonitis with community-acquired disease, the number of isolates of enterococci (23 versus 6) and Enterobacter species (13 versus 4) were increased and the number of isolates of Escherichia coli (21 versus 42) were reduced. Antibiotic therapy before reintervention increased the number of resistant organisms at relaparotomy (33% versus 8%). The in vitro efficacy of the primary antibiotic or combination of drugs did not affect mortality rates (40% versus 38% after effective and ineffective treatment, respectively). Thus, the microbiology of postoperative peritonitis differs significantly from that of community-acquired disease, and specific antibiotic therapy is required, despite the doubtful impact on survival.
Lysophosphatidic acid (LPA) is a small lipid mediator with pleiotropic biological activities, e.g., the regulation of cellular proliferation and various aspects of cellular physiology. Signal transduction is achieved by binding to 2 high-affinity receptors, EDG2 and EDG4, and a group of low-affinity receptors, EDG1-7, all belonging to the superfamily of G protein-coupled receptors. We examined the growth-regulatory effects of LPA in primary cultures of 8 goiters and 1 papillary thyroid cancer. We further assessed mRNA expression of high-affinity receptors EDG2 and EDG4 in 14 normal thyroids, 29 papillary thyroid cancers, 7 follicular thyroid cancers and 13 goiters by quantitative RT-PCR. We also identified mRNA expression of phospholipase A(2) and LPA acyltransferase in fresh thyroid tissues derived from various sources. At concentrations of 10, 50 and 150 microM, LPA induced a 2-fold rise of proliferation (p < 0.001) and acted as strongly as thyrotropin. The combination of LPA and TSH produced significant synergistic effects compared with each substance alone (p < 0.05). Normal thyroid, goiter and papillary or follicular thyroid cancer expressed 2 high-affinity cognate LPA receptors, EDG2 and EDG4. EDG4 receptor mRNA expression was increased 3-fold in differentiated thyroid cancer (p < 0.01), both papillary (p < 0.01) and follicular (p < 0.05), compared to normal thyroid or goiter. Overall expression of EDG2 receptor was unchanged in malignancy; however, increased EDG2 expression in individual samples correlated with lymphonodular metastasis (p = 0.01). Thus, lipid mediators are a novel class of factors involved in the control of proliferation in the human thyroid. Altered mRNA expression of the high-affinity LPA receptor EDG4 suggests a role in the pathogenesis of differentiated thyroid cancer.
In Germany inguinal hernia surgery has changed over the last decade from conventional repairs without alloplastic material to video-assisted minimal invasive techniques or Lichtenstein repair. Since 1991 every patient undergoing inguinal hernia repair has been documented in the North-Rhine area in a routine quality-surveillance study. A total of 173,923 patients with 192,718 groin hernias (85.26% male and 14.74% female) were operated on. In 1993 the Shouldice repair was performed in 54.2%, the Bassini operation in 26%, the transabdominal laparoscopic TAPP repair in only 3.2% of cases. In 1999 the TAPP repair was performed in 13%, the extraperitoneal video-assisted TEP repair in 14%, Lichtenstein repair in 18.5%, Shouldice repair in 35% and the Bassini operation in only 4.8%. The percentage of operations was 13.4% over the last 10 years. However, there was an increase from 12.8% in 1993 to 14.1% in 1997, and a rate of 13.5% in 1999. The following complications were observed: hematoma/seroma formation in 3.78%, wound infection in 1.15%, testicular edema in 0.37% and scrotal edema in 0.64%. The data document the introduction of three new methods for inguinal hernia repair (TAPP, TEP and Lichtenstein repair). A decrease in operations on recurrences is not observed.
Acute inflow stasis of the vena cava superior is an emergency case. Because of the rapidly rising venous pressure, life-threatening complications can arise (e.g. cerebral hemorrhage, hemorrhagic venous infarcts). The main cause of central venous thrombosis is bronchial carcinoma (incidence: 3-5%). Iatrogenic reasons are thrombosis caused by pacemaker electrodes, dialysis catheter, central vein catheters, implanted ports and radiation-induced venous fibrosis. In this case a patient with an esophageal carcinoma was pretreated by a neoadjuvant chemoradiotherapy. The chemotherapy was given through a venous access port, which was implanted earlier. Radiation therapy with a total of 60 Gy followed. After the esophagectomy the patient developed an acute inflow stasis of the vena cava superior.
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BACKGROUND: The purpose of this investigation was to analyze the individual diagnostic and operative strategy in the treatment of medullary thyroid carcinoma (MTC) in international specialized centers and to assess whether standard procedures are carried out in practice everywhere. METHODS: A questionnaire concerning diagnosis and treatment of patients with primary, persistent, or recurrent sporadic or familial MTC was sent to 263 members of the International Association of Endocrine Surgeons. RESULTS: Primary treatment of MTC does not show significant differences for patients with sporadic or familial disease (Chi-square, n.s.), and standard procedures are performed in only 25-40% of patients. Computed tomography scan is the most common localization procedure in persistent or recurrent disease (52-72%), followed by scintigraphy (43-71%), ultrasonography (41-56%), and magnetic resonance imaging (31-49%). In case of negative localization studies, 68-86% of colleagues do not recommend reoperation. In symptomatic patients with stage-IV tumors, however, 84% of colleagues advocate reoperation to provide relief from the tumor burden. CONCLUSIONS: Even with experienced endocrine surgeons, a consensus to uni- and/or bilateral neck dissection in primary MTC is lacking. The majority of authors supports at least total thyroidectomy with central lymph-node dissection. In recurrent disease, there is a general tendency to reoperate in case of positive localization studies and in case of symptomatic disease.
The arterial ketone body ratio is calculated as the ratio of arterial levels of acetoacetate/beta-hydroxybutyrate. It correlates with survival in experimental hemorrhagic shock and outcome after liver surgery and myocardial infarction. Procedures for determination of ketone bodies are often laborious and unreliable. As yet the relationship between results from arterial and venous samples is unclear. We therefore describe the determination of the ketone bodies acetoacetate and 3-hydroxybutyrate by an easy, reliable, rapid, inexpensive enzymatic assay using 3-hydroxybutyrate dehydrogenase (E.C. 1.1.1.30) in a semi-automated setting that does not require deproteinization. Preanalytical parameters, including separation from corpuscular elements within 1 h and storage on ice for less than 1 h, must be strictly observed to avoid rapid decay of acetoacetate by spontaneous decarboxylation. The assay has high sensitivity, specificity (+/-5%), and precision (CV <2.5%) with a measurable range of 5-500 micromol/l for either ketone body, and requires only 23.5 microl of plasma. At temperatures below -17 degrees C plasma may be stored for prolonged periods. Results from prospectively scheduled simultaneous sampling of arterial blood and venous blood from the right atrium in 100 consecutive patients with severe multiple trauma (mean Injury Severity Score 38+/-13) support the view that the lung has no role in ketone body metabolism. We conclude that central venous blood can safely be substituted for arterial blood for determination of the ketone body ratio.
Bone loss in inflammatory bowel disease (IBD) is presumed to be mediated by inflammation. Increased levels of the multifunctional cytokine IL-6 in inflammatory diseases have been proposed to be the link in such "inflammation-mediated osteopenia." A recently described G/C polymorphism with an effect on transcription rate and plasma levels of IL-6 suggests a genetically determined difference in the degree of the IL-6 response to stressful stimuli between individuals. This study aimed to assess the frequency of genotypes and haplotypes of the G/C polymorphism of IL-6 in IBD patients. A further aim was to assess whether carriage of the potentially protective CC genotype is favorable with respect to the development of bone disease in IBD. The IL-6 polymorphism was typed in 105 IBD patients and 113 healthy controls. Bone mineral density was evaluated at baseline and after a prospective 2-year-follow-up. The favorable CC genotype with decreased IL-6 release was not underrepresented in IBD patients compared to healthy controls. Carriage of this genotype was not protective with respect to the development of bone disease, either for the bone mineral density at baseline or for the prospectively observed bone loss. Within the subgroup of patients who did not receive steroids during follow-up, the prospectively observed bone loss was even slightly higher in CC carriers, but differences did not reach significance. Genetically determined differences in the degree of the IL-6 response to stressful stimuli are no major predictors for the degree of bone disease in IBD patients.
INTRODUCTION: From 1986 to 1999 we operated on 963 patients with primary hyperparathyroidism (pHPT). METHODS AND RESULTS: Parathyroid carcinoma was diagnosed clinically and histologically in four patients (0.4%). In two of these patients diagnosis of parathyroid cancer was delayed by misinterpretation of the histopathology leading to an autotransplantation of malignant parathyroid tissue in one case. In two patients multivisceral surgery was performed: beside thyroidectomy, neck dissection, tracheal wall resection and resection of the muscular layer of the oesophagus one patient received oesophagectomy and gastric transposition and one patient a lung wedge resection. Both patients had a temporary palliation of tumour-associated symptoms after multivisceral surgery. The first patient died 2 years after oesophagectomy and 12 years after primary diagnosis from local tumour recurrence and cachexia. The second patient is living with tumour recurrence presenting a serum calcium level of 4.2 mmol/l (normal range 2.0 to 2.5 mol/l) and multiple brown tumours 2 years after lung resection and 6 years after the primary diagnosis. CONCLUSIONS: We conclude that parathyroid carcinomas, being difficult to diagnose, warrant radical surgery, including multivisceral resection to prolong survival and reduce tumour and hypercalcaemia associated symptoms.
BACKGROUND: In contrast with multiple endocrine neoplasia type 2, malignancies are of minor importance in multiple endocrine neoplasia type 1 (MEN 1) syndrome. METHODS: The data for 42 patients with MEN 1 syndrome were evaluated. Twelve patients (29%) had 1 or more associated malignancies: malignant gastrinoma (1 patient), neuroendocrine tumors of the thymus (2 patients), neuroendocrine tumors of the lung (3 patients), neuroendocrine tumor of the ileum (1 patient), adrenocortical carcinomas (2 patients), and a combination of neuroendocrine tumors of thymus, lung or pancreas (3 patients). RESULTS: Despite suspected MEN 1 syndrome in 7 patients, malignancies were detected late in 4 patients and could not be resected curatively. The survival rates for 5 years and 10 years after operation of the malignant tumor were 66% +/- 14% (SE) and 33% +/- 15% (SE), respectively. CONCLUSIONS: In patients at risk for the MEN 1 syndrome, genetic screening is indispensable. Gene carriers have to be followed up closely with hormone analysis and routine examination of the thorax, pancreas, and adrenal glands to detect malignancies as early as possible.